title: Impurity profile study of lopinavir and validation of HPLC method for the determination of related substances in lopinavir drug substance.
abstract: Several related substances (RS4-RS10) were detected in lopinavir drug substance at levels ranging from 0.03% to 0.1% by employing gradient RP-HPLC. The related substances were identified by LC-MS analysis. These related substances were isolated and characterized by Mass, (1)H NMR and FT-IR spectral data. The separation was achieved on a YMC Pack ODS-AQ (250 mm x 4.6 mm, 5 microm) column thermostated at 45 degrees C using 0.02 M KH(2)PO(4) (pH 2.5): acetonitrile as a mobile phase in gradient elution mode. A PDA detector set at 210 nm was used for detection. The investigated validation elements showed the method has acceptable specificity, accuracy, linearity, precision, robustness and high sensitivity with detection limits and quantitation limits ranging from 0.028 microg/ml to 0.063 microg/ml and 0.084 microg/ml to 0.192 microg/ml respectively. The method can be used for routine quality control analysis and stability testing of lopinavir drug substance.
authors.affiliation: APL Research Centre (A Division of Aurobindo Pharma Limited), 313, Bachupally, Hyderabad 500072, Andhra Pradesh, India.
authors.forename: Sreenivasa Rao
authors.initials: SR
authors.lastname: Chitturi
authors.forename: Ch
authors.initials: Ch
authors.lastname: Bharathi
authors.forename: A V Raghava
authors.initials: AV
authors.lastname: Reddy
authors.forename: K Chandrasekhar
authors.initials: KC
authors.lastname: Reddy
authors.forename: Hemant Kumar
authors.initials: HK
authors.lastname: Sharma
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Handa
authors.forename: Ramesh
authors.initials: R
authors.lastname: Dandala
authors.forename: V Hima
authors.initials: VH
authors.lastname: Bindu
mesh_terms: D002021:Buffers; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D004340:Drug Contamination; D004355:Drug Stability; D017408:Guidelines as Topic; D017320:HIV Protease Inhibitors / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D061466:Lopinavir; D013058:Mass Spectrometry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry; D017680:Potassium Compounds / Q000737:chemistry; D011744:Pyrimidinones / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D002021:Buffers; D017320:HIV Protease Inhibitors; D004364:Pharmaceutical Preparations; D010710:Phosphates; D017680:Potassium Compounds; D011744:Pyrimidinones; D014867:Water; D061466:Lopinavir; C013216:potassium phosphate